Chromatograph mass spectrometers including a combination of a chromatograph, such as a gas chromatograph (GC) or a liquid chromatograph (LC), and a mass spectrometer, such as a quadrupole mass spectrometer, are widely used to perform qualitative or quantitative analyses of various components contained in a sample. When a quantitative analysis of known compounds is performed using a chromatograph mass spectrometer, an SIM measurement method is typically used which selectively and repeatedly detects only ions having a specific mass-to-charge ratio m/z or ions including specific mass-to-charge ratios m/z which are previously designated.
When a known compound is quantitatively analyzed using a chromatograph mass spectrometer including a combination of a chromatograph, such as GC or LC, and a triple quadrupole mass spectrometer, an MRM measurement method is used. According to this method, an ion (precursor ion) having a specific mass-to-charge ratio is selected at a first-stage quadrupole mass filter, the ion is dissociated by collision-induced dissociation (CID) in a collision cell, and an ion having a specific mass-to-charge ratio among resultantly generated product ions is selected and detected by a second-stage quadrupole mass filter. The MRM measurement method can remove deleterious effects of irrelevant components through the two-stage quadrupole mass filter. Accordingly, this method has an advantage of improving the S/N ratio and achieving highly sensitive quantitative measurement.
In any case of performing quantitative analysis through SIM measurement or MRM measurement using a chromatograph mass spectrometer, the value of mass-to-charge ratios corresponding to target compounds are required to be set in conformity with the retention times of the target compounds as one measurement condition. For example, chromatograph mass spectrometers described in Patent Literatures 1 and 2 have a function of automatically creating a parameter table representing a measurement condition. After an analysis operator previously creates a compound table including information on measurement target compounds, the parameter table is automatically created based on the information described in the compound table. Such a function of automatically creating a parameter table according to a conventional chromatograph mass spectrometer will be described with reference to a specific example.
FIG. 13 is an example of a compound table. As shown in the diagram, the compound table includes information including the compound name, the predicted retention time, the process time, the mass-to-charge ratio of a quantitative ion, and the mass-to-charge ratio of a confirmation ion for each compound. The quantitative ion is an ion which best characterizes the compound. The confirmation ion is an ion which has another mass-to-charge ratio different from that of the quantitative ion and characterizes the compound. This confirmation ion is typically used to confirm that the chromatogram peak of the quantitative ion originates from the target compound by using the relative ratio between the signal intensity of the confirmation ion peak and the signal intensity of the quantitative ion peak on the mass spectrum. The retention time is the predicted value of the time of elution from a column in the liquid chromatograph. The process time is a parameter for designating a time range during which the compound is measured, where an appropriate time margin is set centering the predicted retention time so as to accommodate the variation in peak width and retention time. Accordingly, even if the retention time of a compound varies, the peak of the compound reliably appears within a range of the retention time of the compound±the process time. FIG. 14 shows the relationship between the peak of a compound on a chromatogram and retention time and process time.
In the process of automatically creating the parameter table according to a measurement method, a measurement time is appropriately divided into segments based on the compound table as described above. A segment is a smallest time unit for setting a measurement condition, such as a condition of target ion or the polarity of target ion to be measured. The measurement condition can be switched on a segment-by-segment basis.
In the conventional process of automatically creating a parameter table, a boundary between segments is automatically set at a time point within an interval between retention times of compounds to be measured is sufficiently large. More specifically, if a conditional expression,[the retention time of a compound X+A]<[the retention time of the compound X+1 having the next longer retention time−A](where A is a process time)  (1)is satisfied, the segment boundary is set at a time point where the elution time range (retention time±A) of the compound X does not overlap with the elution time range of the compound X+1, typically at an intermediate time point between the retention time for the compound X and the retention time for the compound X+1, and thus the measurement time is divided into different segments by the segment boundary.
FIG. 15A and FIG. 15B show chromatograms illustrating a segment dividing method. As shown in FIG. 15A, if the elution time ranges of the compound X and the compound X+1 overlap with each other, no segment boundary is set. That is to say, in this case, the compound X and the compound X+1 belong to the same segment. Meanwhile, as shown in FIG. 15B, if the elution time ranges of the compound X and the compound X+1 do not overlap with each other, a segment boundary is determined between the retention time of the compound X and the retention time of the compound X+1. Thus, the compound X and the compound X+1 belong to different segments. According to such an algorithm, segments can be defined for all the compounds (or some compounds designated by an analysis operator) listed in the compound table.
FIG. 16 shows one example of a parameter table of a measurement method automatically created based on the compound table shown in FIG. 13. In the parameter table, the measurement condition for one compound is listed as a “measurement event” on one row. Each measurement event lists, besides the compound name, the number of a segment where the compound is measured (hereinafter, the segment number is indicated by “#”), the measurement start time, the measurement end time, the event time, the mass-to-charge ratio of the ion to be measured, and the dwell time. In the mass-to-charge ratio of the ion to be measured, the mass-to-charge ratio m/z-1 of the quantitative ion and the mass-to-charge ratio m/z-2 of the confirmation ion of the compound to be measured are set. The measurement start time and the measurement end time are the start time and the end time of the segment. The event time is a unit time of repetition of the measurement event. The dwell time is the time during which the detector actually receives and accumulates ions, that is, data collection time.
In the example in FIG. 13 and FIG. 16, a time interval sufficiently satisfying the conditional expression (1) exists between a compound T and a compound U having the next longer retention time. Accordingly, a segment boundary is set there. Segment #1 and segment #2 are created before and after the boundary. Compounds A to T are assigned to be measured in the time period of segment #1 whose measurement start time is 10.000 [min] and measurement end time is 11.458 [min]. FIG. 5 is a schematic diagram showing the relationship of segments and compounds with time as abscissa.
The event time is automatically calculated from a preset measurement point time interval, which is called a loop time, and the number of compounds measured in one segment. FIG. 16 shows an example where the loop time is set to 300 [msec]. The ions originating from each compound need to be measured at an interval of a loop time of 300 [msec]. Since the number of compounds to be measured in segment #1 is 20, the event time allotted to each compound is 300 [msec]/20=15 [msec]. Meanwhile, in segment #2, the compound to be measured is the compound U alone, and the same loop time 300 [msec] is allotted as the event time.
As described above, the dwell time is the time during which the detector actually captures ions. The event time includes, in addition to the dwell time, wait time (hereinafter, called “voltage stabilization wait time”) for stabilizing the voltage after the voltage applied to a quadrupole mass filter is changed. The dwell time also depends on the number of ions to be measured in one event time. Accordingly, the dwell time Td for each ion is calculated by the following equation (2).Td=(event time−voltage stabilization wait time)/[the number of ions to be measured]  (2)In the example of FIG. 16, the voltage stabilization wait time per ion to be measured is set to 1 [msec]. As a result, the dwell time Td for each ion is (15−1×2)/2=6.5 [msec]
If the dwell time is too short, unfavorable effects of external factors, such as drift and noise, tend to be included in signal intensity data acquired by the detector, making it difficult to achieve sufficient measurement reproducibility. Accordingly, accurate quantitative measurement requires an adequate length of dwell time. To secure an adequate dwell time, the event time is required to be long. And it is preferred to increase the number of segments to reduce the number of compounds to be measured allotted to one segment. However, the aforementioned conventional algorithm of automatically creating a parameter table cannot finely set segments, and many compounds are allotted to one segment, if there are many compounds having retention time close to each other. As a result, the dwell time for each ion is necessarily shortened, which may incur reduction of the accuracy of quantitative measurement because sufficient measurement reproducibility and measurement sensitivity cannot be achieved. According to the example in FIG. 13 and FIG. 16, the compounds A to T are allotted to one segment, which resultantly reduces the dwell time.
On the other hand, to secure a long dwell time, an analysis operator (user) can finely divide segments through manual operation. However, if segments are just finely divided, a part of elution time range defined by retention time±A of some compounds may trespass the segment boundary, and data cannot be collected in the part of the elution time range. In such a case, if the retention time of the compound changes owing to an influence of a minor component or the like (i.e., if the peak position shifts as indicated by broken lines in FIG. 14), a part of the peak corresponding to the compound on the chromatogram is eclipsed and the peak area cannot be accurately measured. Accordingly, quantitative accuracy is substantially reduced.
It is possible to set a long loop time to secure long dwell time. However, if the loop time is set long, the measurement time interval elongates, and the number of data points constituting one peak is reduced. As a result, the peak top cannot be correctly determined, and the shape of curve is not adequately detected at the rising part and the falling part of the peak. The problems reduce the detection accuracy of the peak area, and deteriorates the quantitative measurement.